Study of the Efficacy and Safety of MEDI4893 (SAATELLITE)

A Phase 2 Randomised, Double-blind, Placebo-controlled, Single-dose, Dose-ranging Study of the Efficacy and Safety of MEDI4893, a Human Monoclonal Antibody Against Staphylococcus Aureus Alpha Toxin in Mechanically Ventilated Adult Subjects.

Clinical trial looking at safety and efficacy of MEDI4893 in prevention of pneumonia caused by Staphylococcus aureus in high-risk patients

Study Overview

• Status: Completed
• Conditions: Staphylococcus Aureus Pneumonia
• Intervention / Treatment: Drug: MEDI4893; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 213
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Arlon, Belgium, 6700
    • Research Site
  • Bruxelles, Belgium
    • Research Site
  • La Louvière, Belgium, 7100
    • Research Site
  • Lodelinsart, Belgium, 6042
    • Research Site
  • Yvoir, Belgium, 5530
    • Research Site
• Czechia
  • Brno, Czechia, 656 91
    • Research Site
  • Decin, Czechia, 405 99
    • Research Site
  • Kyjov, Czechia, 697 01
    • Research Site
  • Praha, Czechia, 128 08
    • Research Site
  • Teplice, Czechia, 415 29
    • Research Site
• France
  • Angers CEDEX 9, France, 49933
    • Research Site
  • Clermont-ferrand, France, 63003
    • Research Site
  • Garches, France, 92380
    • Research Site
  • Grenoble Cedex, France, 38043
    • Research Site
  • Le Chesnay, France, 78157
    • Research Site
  • Lille Cedex, France, 59037
    • Research Site
  • Limoges, France, 87042
    • Research Site
  • Lyon, France, 69394
    • Research Site
  • Nantes, France, 44093
    • Research Site
  • Orléans Cedex 2, France, 45100
    • Research Site
  • Pierre Benite Cedex, France, 69495
    • Research Site
  • Poitiers, France, 86201
    • Research Site
  • Rennes, France, 35033
    • Research Site
  • Tours, France, 37044
    • Research Site
• Germany
  • Berlin, Germany, 12351
    • Research Site
  • Berlin, Germany, 13353
    • Research Site
  • Erfurt, Germany, 99089
    • Research Site
  • Heidelberg, Germany, 69120
    • Research Site
  • Jena, Germany, 07740
    • Research Site
• Greece
  • Alexandroupolis, Greece, 68100
    • Research Site
  • Athens, Greece, 14564
    • Research Site
  • Ioannina, Greece, 455 00
    • Research Site
  • Larissa, Greece, 41110
    • Research Site
  • Larissa, Greece, 41221
    • Research Site
• Hungary
  • Kistarcsa, Hungary, 02143
    • Research Site
  • Vác, Hungary, 2600
    • Research Site
• Portugal
  • Ponte De Lima, Portugal, 4990-041
    • Research Site
• Spain
  • Barcelona, Spain, 08035
    • Research Site
  • Barcelona, Spain, 08036
    • Research Site
  • Getafe, Spain, 28905
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Oviedo, Spain, 33011
    • Research Site
  • Terrassa, Spain, 08221
    • Research Site
  • Valencia, Spain, 46026
    • Research Site
  • Valencia, Spain, 46014
    • Research Site
• Switzerland
  • Geneva, Switzerland, 1211
    • Research Site
  • Lausanne, Switzerland, CH-1011
    • Research Site
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Colonized with Staphylococcus aureus, expected to require prolonged intubation and mechanical ventilation, without any evidence of active pneumonia.

Exclusion Criteria:

• Staphylococcal disease at randomisation; lung injury score consistent with pneumonia; current lung disease; chronic tracheostomy patients; currently receiving systemic anti-staphylococcal antibiotics; moribund patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MEDI4893 5000 mg; Participants will receive a single intravenous (IV) dose of MEDI4893 5000 milligrams (mg) on Day 1 of the study.	Drug: MEDI4893; Participants will receive a single IV dose of MEDI4893 2000 or 5000 mg on Day 1 of the study.
Placebo Comparator: Placebo; Participants will receive a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.	Other: Placebo; Participants will receive a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.
Active Comparator: MEDI4893 2000 mg; Participants will receive a single IV dose of MEDI4893 2000 mg on Day 1 of the study.	Drug: MEDI4893; Participants will receive a single IV dose of MEDI4893 2000 or 5000 mg on Day 1 of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Endpoint Adjudication Committee-Determined (EAC) Staphylococcus Aureus (S Aureus) Pneumonia	The EAC S aureus pneumonia was based on clinical, radiographic, and microbiologic criteria. Clinical criteria: 1 major criteria (PaO2/FiO2 ratio < 240 mmHg maintained for at least 4 hours or decrease in PaO2/FiO2 by >= 50 mmHg maintained for at least 4 hrs or a need to initiate non-invasive mechanical ventilation or re-initiate invasive mechanical ventilation because of respiratory failure or worsening of respiratory status); and at least 2 of minor criteria (systemic signs of infection, production of purulent sputum/endotracheal secretions, new onset of cough, physical examination findings consistent with pneumonia/pulmonary consolidation, dyspnea, and/or tachypnea). Radiographic criteria: new or worsening infiltrate consistent with pneumonia on chest X-ray obtained within 24 hrs of event. Microbiologic criteria: at least 1 culture positive for S aureus (respiratory specimen, or blood, or pleural fluid aspirate or lung tissue culture during episode of pneumonia).	Day 1 through Day 31
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Through 31 Days	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.	Day 1 through Day 31
Number of Participants With TEAEs Through 91 Days	An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.	Day 1 through Day 91
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs)	A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.	Day 1 through Day 191
Number of Participants With Adverse Events of Special Interest (AESIs)	An AESI is one of scientific and medical interest specific to understanding of the study drug and may have required close monitoring and rapid communication by the investigator to the sponsor. An AESI may have been serious or non-serious.	Day 1 through Day 191
Number of Participants With New Onset Chronic Diseases (NOCDs)	An NOCD defined as a newly diagnosed medical condition that is of a chronic, ongoing nature. It is observed after receiving the study drug and is assessed by the investigator as medically significant.	Day 1 through Day 191

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Serum Concentration (Cmax) of MEDI4893	Maximum observed serum concentration (Cmax) of MEDI4893 is reported.	Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, 31, 61, and 91
Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0-Last]) of MEDI4893	Area under the serum concentration time curve from time zero to last measurable concentration (AUC[0 - Last]) of MEDI4893 is reported.	Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, 31, 61, and 91
Observed Serum Concentration of MEDI4893 Through 30 Days Post Dose (C30)	Observed serum concentration of MEDI4893 through 30 days post dose (C30) is reported. Serum concentration of MEDI4893 through 30 days post dose accounted the overall concentration of MEDI4893 measured on specified time points (Days 1, 4, 8, 15, 22, and 30).	Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, and 30
Observed Serum Concentration of MEDI4893 Through 90 Days Post Dose (C90)	Observed serum concentration of MEDI4893 through 90 days post dose (C90) is reported. Serum concentration of MEDI4893 through 90 days post dose accounted the overall concentration of MEDI4893 measured on specified time points (Days 1, 4, 8, 15, 22, 31, 61, and 91).	Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, 31, 61, and 90
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to MEDI4893	Participants with ADA-positive at any of Day 31, Day 61, or Day 91 post-baseline assessments were always counted as "positive" at post-baseline.	Pre-dose on Day 1 (Baseline); and on Days 31, 61, and 91

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Innovative Medicines Initiative and COMBACTE-NET; Antibacterial Resistance Leadership Group

Publications and helpful links

General Publications

• François B, Jafri HS, Chastre J, Sánchez-García M, Eggimann P, Dequin PF, Huberlant V, Viña Soria L, Boulain T, Bretonnière C, Pugin J, Trenado J, Hernandez Padilla AC, Ali O, Shoemaker K, Ren P, Coenjaerts FE, Ruzin A, Barraud O, Timbermont L, Lammens C, Pierre V, Wu Y, Vignaud J, Colbert S, Bellamy T, Esser MT, Dubovsky F, Bonten MJ, Goossens H, Laterre PF; COMBACTE Consortium and the SAATELLITE Study Group. Efficacy and safety of suvratoxumab for prevention of Staphylococcus aureus ventilator-associated pneumonia (SAATELLITE): a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial. Lancet Infect Dis. 2021 Sep;21(9):1313-1323. doi: 10.1016/S1473-3099(20)30995-6. Epub 2021 Apr 21.
• Yu XQ, Robbie GJ, Wu Y, Esser MT, Jensen K, Schwartz HI, Bellamy T, Hernandez-Illas M, Jafri HS. Safety, Tolerability, and Pharmacokinetics of MEDI4893, an Investigational, Extended-Half-Life, Anti-Staphylococcus aureus Alpha-Toxin Human Monoclonal Antibody, in Healthy Adults. Antimicrob Agents Chemother. 2016 Dec 27;61(1):e01020-16. doi: 10.1128/AAC.01020-16. Print 2017 Jan.

Helpful Links

• CD-ID-MEDI4893-1139 Protocol amendment 5_redacted_FINAL_APPROVED
• CD-ID-MEDI4893-1139 Statistical Analysis Plan_Final v4.0_Redacted_FINAL_APPROVED

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2014
• Primary Completion (Actual): October 2, 2018
• Study Completion (Actual): October 2, 2018

Study Registration Dates

• First Submitted: October 30, 2014
• First Submitted That Met QC Criteria: November 17, 2014
• First Posted (Estimate): November 20, 2014

Study Record Updates

• Last Update Posted (Actual): December 23, 2019
• Last Update Submitted That Met QC Criteria: December 11, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Staphylococcal Infections; Pneumonia, Bacterial; Pneumonia, Staphylococcal
• Other Study ID Numbers: CD-ID-MEDI4893-1139

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No